Dr. Ambinder: So, there is a concern for higher false positives and over detection rate?
Dr. Sprenkle: Not higher. So, it’s not a higher false policy rate. So it’s still a lower false positive rate, but false positives still do occur. So, there still is a rate of false positives. Depending on which study, it seems to be between six and maybe 15%, but that is still significantly lower. The false positive rate for CT or bone scan is at least 30% for most of those. So, while it still exists, it is lower than the conventional imaging.
Dr. Ambinder: Understood. And I know that initially people were concerned with whether PSMA we’d be seeing things because we’re seeing things a little bit more sensitive. Are we also going to over detect? What are your thoughts on that?
Dr. Sprenkle: So, it really depends on what you mean by over detection. I think that’s the quintessential clinical question is now that we are detecting more of these metastases, are we avoiding curative treatment for example, in people who would benefit from it because we detect a microscopic metastasis? To try to tease that out, some of the studies have looked at really only quantifying lymph nodes that are five millimeters or larger versus smaller than five millimeters. The detection rates are different. Honestly, if there’s cancer outside the prostate, I think you’d need to know that. This is happening in conjunction though with many moves towards treating metastatic prostate cancer with localized treatment. So, these things are all happening at once, but we are considering men with metastatic disease potentially still candidates for local therapy.
And especially in the case of lymph node metastases which can be resected surgically, I’m not sure that’s a huge difference. So, back to your question of over detection, it really depends on how we define that. So, what is that and what does that detection mean? We can’t compare outcomes in terms of presence of metastasis and presence of recurrence. We can’t compare PSMA detected rates to those under conventional imaging. I think that would be disingenuous because we are detecting much more disease with PSMA PET. Much more disease may be an exaggeration, but it’s different, we’re measuring things differently. So, I think we are detecting differently. Is it are we detecting too much? It kind of depends. With more accurate imaging, we’re able to more accurately stratify people’s risk and decide and instead of maybe saying, it have to be metastasis free, maybe if they have low volume disease detected on PSMA PET, those are still candidates for definitive therapy versus otherwise.
Dr. Ambinder: And so has PSMA and maybe you can give us an example of a patient you either saw, or someone you had a discussion with, of where would change management?
Dr. Sprenkle: So, it definitely changes management. I think it makes us more comfortable treating people locally if they have a negative imaging. So, people could have really high risk disease and we’re worried about doing a surgical approach, but we do a PSMA PET and they have negative imaging or imaging that only identifies cancer in the prostate, we feel more comfortable doing a surgery on those patients because the likelihood of them having occult metastatic disease is much lower than would be potentially the case with conventional imaging. We also see this, specifically, you can have a case where you do see a positive lymph node and it’s outside of your typical lymph node dissection and you would then be able to include that in your lymph node dissection.
So, it may not change your decision on whether or not to have surgery or perform surgery, but with counseling appropriately, the patient that the likelihood of cure may be a little bit lower, but you can go after that lymph node and get all the visible disease. Also, in when in an area of interest that’s in, I think there are a couple different clinical trials looking at this in the setting of biochemical recurrence.
So, in men who have had their prostates removed, they have a rising PSA, PSMA PET can really help determine should they be getting pelvic radiation or not or pelvic radiation plus a boost to an area of visible recurrence, either in the pelvis or outside the pelvis. So, I think we’re getting a lot more anatomic information about prostate cancer and where it is with this imaging technology.
Dr. Ambinder: That’s awesome and I think potentially my final question, but PSMA is definitely one of those things in prostate cancer that has been very exciting. We have so many different areas over the last 20 years of definitely very advanced changes in a small amount of time. PSMA is definitely looking like that and we know about PSMA targeted therapies. Is there any other futuristic things that we’re looking for that PSMA is going to be that stepping stool that we needed for?
Dr. Sprenkle: I think that’s a great question. Obviously as you mentioned, the theronostic treatments with PSMA linked radiation therapy, those are in trials and showing significant benefit in the patients that are receiving that treatment. I think as a urologist, my interest is in the initial diagnostic space and active surveillance and management patients will localize disease. I think those are two areas where we’re starting to see interest in potentially some clinical trials, but can men avoid a prostate biopsy for example, with the right clinical parameters? There have been a couple recent publications of isolated series looking at just using a PSMA and an MRI and with those two imaging tests going straight to surgery without doing a biopsy, I think that’s still controversial. We need a lot more data that may be bringing in a little too much of an unknown, more variability than we want, but realistically, even when prostate biopsy attack cancer or not, depends on how comfortable you are with the Gleason grading and how important we feel that is in patient’s long term outcomes.
Similarly in active surveillance using PSMA PET, the reason that it’s interesting there is, it does not really light up with benign prostate cancer and Gleason six doesn’t really light up. It really is pretty definitive or it has better discrepancy for intermediate or higher risk disease than for example, MRI. So, other areas of significant interest are MRI fusion PET, or sorry, PSMA fusion with MRI and how we can leverage that. The early studies, some of them are interesting. It shows that high grade high risk lesions on MR correlate with high suspicion on PSMA PET. So, I think we still have some work to do there, but especially with the introduction or the growing use of AI and big data and some of the improved mathematical analysis technologies that we have, there’s a lot of room I think for improvement and potentially really changing the way that we diagnose and image prostate cancer.
Dr. Ambinder: That’s wonderful. Dr. Sprenkle, I want to thank you again for your time. Every time we’ve had you, we’ve learned a lot and I think we’re going to have you again. We have some more topics in early prostate cancer to talk to you about.
Dr. Sprenkle: Sounds great. Looking forward to. Thanks, David.